E3 Ligase Ligandalyzer: A Structure-First, Ligand-Centric Platform for E3 Ligase Recruiter Selection

Abstract

Here, we present E3 Ligase Ligandalyzer Version 1.0, a freely accessible, recruiter-centric web platform for comparative exploration of experimentally resolved E3 ligase-recruiter complexes. The locked Version 1.0 dataset spans 35 E3 ligases, 604 reconciled recruiter entities, and 1,372 active structure-specific recruiter instances across 685 experimentally resolved PDB structures. Recruiters are linked to normalized chemical representations and analyzed using cheminformatics and structure-based workflows to compute physicochemical descriptors, scaffold relationships, aligned binding-pocket views, and solvent-accessible surface area patterns relevant to linker attachment. The platform integrates recruiter-entity, recruiter-instance, scaffold, and ligase views, allowing users to compare experimentally grounded chemical and structural observations without imposing predictive rankings. The platform supports direct transition into downstream degrader-design workflows, including integration with PROTAC Builder (protacbuilder.com). E3 Ligase Ligandalyzer is freely available at https://e3ligandalyzer.com, and the associated code and dataset-generation scripts are available at https://github.com/schurerlab/E3-Ligandalyzer-Scripts.